Mass spectrometry has proven to be an effective analytical technique for identifying unknown compounds and for determining the precise mass of known compounds. Advantageously, compounds can be detected or analysed in minute quantities allowing compounds to be identified at very low concentrations in chemically complex mixtures. Not surprisingly, mass spectrometry has found practical application in medicine, pharmacology, food sciences, semi-conductor manufacturing, environmental sciences, security, and many other fields.
A typical mass spectrometer includes an ion source that ionizes particles of interest. The ions are passed to an analyser region, where they are separated according to their mass (m)-to-charge (z) ratios (m/z). The separated ions are detected at a detector. A signal from the detector may be sent to a computing or similar device where the m/z ratios may be stored together with their relative abundance for presentation in the format of a m/z spectrum.
Typical ion sources are detailed in “Ionization Methods in Organic Mass Spectrometry”, Alison E. Ashcroft, The Royal Society of Chemistry, UK, 1997; and the references cited therein. Conventional ion sources may create ions by atmospheric pressure chemical ionisation (APCI); chemical ionisation (CI); electron impact (EI); electrospray ionisation (ESI); fast atom bombardment (FAB); field desorption/field ionisation (FD/FI); matrix assisted laser desorption ionisation (MALDI); or thermospray ionization (TSP).
Ionized particles may be separated by quadrupoles, time-of-flight (TOF) analysers, magnetic sectors, and Fourier transform and quadrupole ion traps. Most ion sources are capable of producing ionized particles of positive or negative in polarity. For example, ESI transfers ions that are created in an acidic or basic solution directly into the gas phase. These ions are typically products of acid base reactions, such as protonated molecular adducts that tend to have basic sites, or negatively charged ions that are slightly acidic. APCI creates negative or positive ions in the gas phase, through chemical reactions.
The ion detector in a mass spectrometer typically amplifies the ion signal striking a detection surface in order to provide sufficient signal-to-noise to measure intensity as a function of mass. Typical ion detectors include discrete electrodes with a resistive chain or a continuous channel with a resistive surface. Ions strike the first electrode, causing secondary electrons to be emitted from the surface and undergo a cascade of amplification as they are accelerated down the tube. The electron acceleration potential is the difference between the voltage on the first electrode and the last electrode.
The emission of secondary electrons is velocity dependent, with higher velocity ions producing more emission. Ions of different mass-to-charge ratios are accelerated to the same energy (for the same charge state), and since E=1/2 mv2 the velocities and therefore the detection efficiency is mass dependent.
Two common approaches to detection are used: pulse counting and analog current detection. In pulse counting detection, individual ion pulses are amplified, typically with a gain between 1×106 and 100×106, and detected as a current pulse. In analog current detection, the individual ion pulses are amplified with a gain between 1,000 and 10,000 and measured as a DC current.
In some applications such as pharmaceutical drug discovery and drug development, it is desirable to investigate both positive and negative ions generated by one or more ion sources at approximately the same time. Therefore the mass analyser and ion detector must be able to rapidly switch from a mode that samples one polarity (e.g. negative ions) to another (e.g. positive ions).
Such switching typically requires reversal of polarity of large applied voltages. To do so, a power supply having a high voltage range that is capable of quick switching is required. Moreover, extreme care must be taken to limit the noise resulting from power supply switching, and to ensure the output signal is not distorted, and that the detector is not damaged. Typically, providing a suitable supply and integrating it in an ion detector is costly, and complex.
At least one ion detector that may be used to simultaneously detect both positively and negatively charged ions uses two conversion electrodes (also referred to as dynodes). Incoming positive ions strike one conversion electrode, held at high negative voltage, causing ejection of electrons. Incoming negative ions are attracted to, and strike the second conversion electrode, held at high positive voltage, causing ejection of a positive ion. Positive ions, and electrons emitted by the conversion electrodes are attracted to, and strike the inlet of a glass or similar electron multiplier, that is kept at a voltage above that of the conversion electrodes. Incident ions and electrons cause the emission of electrons, within the multiplier. Measurement of emitted electrons and associated energies allows for detection of ions incident on the conversion electrodes.
By design, emitted electrons are detected at ground potential, and may thus be detected by an analog detector. Not surprisingly, conversion of ions to electrons at electrodes is dependent on the mass of the ions. Unfortunately, conversion of negative to positive ions at a conversion electrode is not well understood and may exhibit poor sensitivity for certain compounds. Thus, negative ion detection in such a detector is mass and compound dependent.
Further, as positive ions are heavier than electrons, the electrons are accelerated more quickly to the multiplier, than positive ions. The relatively slow speed of the positive ion can impede high speed operation of the detector.
Accordingly, there is a need for an improved ion detector, and method capable of quickly and efficiently detecting both positively and negatively charged ionized particles.